A metal-organic framework material based on dithienyloctacarboxylic acid ligand

Abstract

This patent designs and synthesizes a metal-organic framework material—Co-TBTT—based on the dithienyloctacarboxylic acid ligand, and uses it as a non-enzymatic glucose electrochemical sensing material for glucose detection. Its potential in glucose sensing was evaluated through electrochemical performance testing. Experimental results show that the Co-TBTT-modified electrode exhibits excellent electrochemical response to glucose under enzyme-free conditions, with a linear detection range of 13.5 μM to 3 mM and a detection limit as low as 0.20 μM, outperforming most currently reported enzyme-free glucose sensors. The Co-TBTT electrode in the presence of Na... + K + Even in mixed solutions containing coexisting ions and interfering substances such as uric acid (UA), ascorbic acid (AA), and dopamine (DA), it maintains good anti-interference ability and exhibits strong selectivity. These excellent properties can be attributed to the porous structure and abundant metal active sites of the Co-TBTT material, providing a novel functional material for the electrochemical sensor detection of glucose.

Description

[0001] This invention belongs to the fields of metal-organic framework materials, biomedical analysis and detection, and electrochemical sensing technology, and provides an electrochemical sensor for detecting glucose, as well as its preparation method and detection method. Background Technology

[0002] Glucose, as a core monosaccharide in the energy metabolism of vital activities, is closely related to the development of diabetes due to its homeostasis imbalance. According to the International Diabetes Federation (IDF), approximately 9.5% of the global population is affected by diabetes, and this number is projected to surge to 578 million adults by 2030. Long-term hyperglycemia-induced metabolic disorders can lead to serious complications such as cardiovascular disease, kidney failure, and retinopathy. Clinically, a blood glucose concentration deviating from the normal range (3.9-7.0 mM) signifies an extremely high risk of complications. Since diabetes is currently incurable, developing technologies that can monitor blood glucose levels in real time and with precision is crucial for developing individualized treatment plans and managing the course of the disease.

[0003] Currently, glucose detection technologies encompass various pathways, including acoustic, magnetic, and optical sensors. Among these, electrochemical sensing technology captures the redox signals of target molecules through highly selective recognition units and converts them into quantified current responses, offering significant advantages such as fast response, low cost, and ease of miniaturization. However, traditional enzymatic glucose sensors are susceptible to limitations imposed by environmental temperature, humidity, pH, and enzyme activity, resulting in poor stability. In contrast, enzyme-free glucose sensors utilize nanomaterials to directly electrocatalyze the oxidation of glucose, effectively overcoming the inherent limitations of biological enzymes and becoming a research hotspot in recent years.

[0004] Among numerous electrocatalytic materials, metal-organic frameworks and their derivatives exhibit outstanding electrocatalytic activity and long-term stability due to their highly tunable pore structure, ultra-high specific surface area, and abundant active sites.

[0005] This invention utilizes a functionalized ligand or multi-metal center strategy to significantly improve the electron transport rate and chemical stability of MOF materials in alkaline electrolytes. Combined with electrochemical detection technology, the sensor prepared using this approach not only meets the stringent clinical requirements for low limits of detection (LOD) but also possesses extremely high sensitivity and specificity. This technological approach provides an ideal material platform for developing high-performance, low-cost portable blood glucose monitoring devices, and has broad application prospects in clinical diagnostics and home health management. Summary of the Invention

[0006] The purpose of this invention is to provide an enzyme-free glucose electrochemical sensor based on dithienyloctacarboxylic acid MOFs and its preparation method, to address the problems of low sensitivity or insufficient electrocatalytic activity in glucose detection of existing electrochemical sensors. To achieve this goal, this invention designed and synthesized a novel dithienyloctacarboxylic acid MOF material and modified it onto the surface of a working electrode to construct an enzyme-free glucose electrochemical sensor. Subsequently, the glucose response performance of the modified electrode was evaluated in detail using an electrochemical workstation. Experimental results show that the Co-TBTT modified electrode exhibits excellent performance in enzyme-free glucose sensing. Compared with existing technologies, the sensor prepared in this invention not only has extremely high sensitivity and stability, but its performance also surpasses most reported enzyme-free glucose sensing electrodes, and it can efficiently detect glucose concentration under alkaline conditions.

[0007] Technical solution:

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] The preparation method of the enzyme-free glucose electrochemical sensor of the present invention is as follows: First, a material is modified on a glassy carbon working electrode, and a standard three-electrode system is constructed using a CHI760E electrochemical workstation. This three-electrode system consists of a 3 mm diameter glassy carbon working electrode, a silver / silver chloride reference electrode, and a platinum wire counter electrode. A 0.1 mol / L NaOH solution is used as the test solution. Before testing, nitrogen gas is continuously bubbled into the electrolytic cell for 30 minutes to effectively remove the interference of dissolved oxygen on the background current. Within a potential range of 0 to +0.6 V, a scan rate of 50 mV / s is set, and cyclic voltammetry (CV) curves are recorded to determine the characteristic peak potential of the material for glucose oxidation. By analyzing the current response change pattern, the enzyme-free glucose sensing performance of the modified electrode in an alkaline environment is systematically evaluated until stable test data is obtained, thus completing the electrode performance test.

[0010] The experiment used a CHI760E electrochemical workstation. The standard three-electrode system included a 3 mm diameter glassy carbon working electrode, a platinum wire counter electrode, and a silver / silver chloride reference electrode. The blank solution was a 0.1 mol / L NaOH strongly alkaline solution. Before testing, the system was bubbled with high-purity nitrogen for 30 minutes to effectively remove dissolved oxygen and eliminate background interference from its reduction peak on the weak signal. The voltammetric scan program was run within a low potential window of -0.1 V to 0.2 V at a scan rate of 50 mV / s. The electrochemical sensing capability of the electrode for glucose was evaluated by continuously adding glucose standard solution.

[0011] Compared to existing enzyme-free glucose sensors, the sensor of this invention demonstrates higher detection accuracy and stronger anti-interference capabilities in practical applications. Furthermore, this sensor can efficiently detect glucose concentration in alkaline environments, showing broad application prospects. Attached Figure Description

[0012] Figure 1 This is a CV comparison chart of glucose detection using an electrochemical sensor in this invention. The black curve is the CV chart of the bare electrode, and the red curve is the CV chart of the electrode modified with Co-TBTT particles.

[0013] Figure 2 Optimization of MOF dropping conditions for Co-TBTT / GCE

[0014] Figure 3 'a' represents the CV curves of Co-TBTT / GCE at different scan rates; Figure 3 b is Figure 3 The linear fitting curve of a

[0015] Figure 4 Figure 'a' shows the DPV of Co-TBTT / GCE with continuous addition of glucose in 0.1 mol / L NaOH; Figure 4 b is Figure 4 The linear fitting curve of a

[0016] Figure 5 For the selection study (a), repeatability study (b), and stability study (c) of Co-TBTT / GCE. Detailed Implementation

[0017] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in these embodiments. Unless otherwise specified, the experimental materials used in the following embodiments were purchased from conventional biochemical reagent stores.

[0018] Example 1

[0019] Preparation of Co-TBTT particles:

[0020] Co(NO3)2·6H2O (8 mg, 0.027 mmol) and TBTT-8COOH (5 mg, 0.0063 mmol) were dissolved in 1.5 mL of DMA. After sonication, 0.75 mL of H2O and 75 μL of acetic acid were added. The mixture was placed in a 100 °C oven for 36 h and then cooled to room temperature. The crystals were collected by filtration, washed with DMA and ethanol, and dried in air to obtain dark purple crystals.

[0021] Example 2

[0022] Construction of a glucose sensor:

[0023] Glassy carbon electrode (GCE) was polished with 0.05 µm alumina powder, then ultrasonically cleaned sequentially with anhydrous ethanol and ultrapure water, and air-dried after cleaning. This was used for material drop-coating modification and subsequent electrochemical performance studies. A selected Co-TBTT sample was ground and ultrasonically dissolved in deionized water to obtain a homogeneous solution of 1 mg / mL. 10 μL of this solution was dropped onto the treated GCE surface, dried at room temperature, and then 5 μL of 0.05 wt% Nation solution was added to the GCE surface to obtain the final Co-TBTT / GCE modified electrode.

[0024] Example 3

[0025] Electrocatalytic performance of Co-TBTT on glucose:

[0026] To evaluate the electrocatalytic performance of the prepared modified electrode, cyclic voltammetry (CV) was used in 0.1 mol / L NaOH electrolyte, with a scan range of 0–0.6 V and a scan rate of 50 mV / s, to investigate the electrochemical behavior of the electrode in the presence and absence of glucose. Figure 1 As shown, in blank NaOH solution, the bare glassy carbon electrode did not exhibit obvious redox characteristic peaks, indicating its lack of electrochemical activity within the test potential range. In contrast, the Co-TBTT / GCE electrode displayed a pair of redox peaks (oxidation peak potential Epa≈0.35 V, reduction peak potential Epc≈0.25 V), which is attributed to the interconversion of Co²⁺ and Co³⁺ under alkaline conditions.

[0027] Upon further introduction of 1 mM glucose, the voltammetric curve of the bare GCE showed almost no change compared to the blank solution, indicating that the bare electrode has no catalytic effect on glucose oxidation. However, the Co-TBTT / GCE exhibited a significant redox response in the presence of glucose, and the substantial increase in the oxidation current signal demonstrated that this material possesses excellent electrocatalytic oxidation ability for glucose molecules.

[0028] Example 4

[0029] Material optimization:

[0030] To achieve optimal sensor detection performance, the materials were optimized, and the modification amount of the Co-TBTT material was adjusted. For example... Figure 2 As shown, the optimal modification amount of the best Co-TBTT material is 10 μL.

[0031] Example 5

[0032] Between scan rates of 10 mV / s and 200 mV / s, the anodic peak current of the redox peak gradually increases with the scan rate, such as... Figure 3 As shown in Figure a. By plotting the relationship between the peak current value and the square root of the scan rate, it can be seen that as the scan rate increases, the linear relationship between the corresponding peak current value and the square root of the scan rate is good, as shown in Figure a. Figure 3 As shown in Figure b, the linear correlation coefficient between the peak current value and the square root of the corresponding scan rate is 0.995. According to previous literature reports, the glucose oxidation process of the fabricated glucose sensor Co-TBTT / GCE is a typical diffusion-controlled process.

[0033] Example 6

[0034] Electrochemical detection of glucose:

[0035] Glucose analysis was performed on Co-TBTT / GCE using differential pulse voltammetry. Under optimal conditions, glucose solution was continuously added to 0.1 mol / L NaOH solution, and the current response was recorded. Figure 4 As shown in Figure a, the response current gradually increases with the addition of glucose. Figure 4 b shows the corresponding calibration curve (y = 0.10x + 2.72, R). 2 =0.996), linear range of 13.5 μM to 3 mM, sensitivity of 141.4 μA mM. -1 cm -2 The detection limit was 0.20 μM (S / N=3).

[0036] Example 7

[0037] Selectivity, repeatability and stability studies:

[0038] To evaluate the specificity of Co-TBTT as a glucose mimicry enzyme, this experiment involved adding 1 mM glucose and equal concentrations of common interfering agents (Na⁺, K⁺, ascorbic acid AA, uric acid UA, and dopamine DA) sequentially to a 0.1 mol / L NaOH electrolyte, and detecting the current response using differential pulse voltammetry (DPV). Figure 5 As shown in Figure a, apart from the significant oxidation current caused by glucose, other interfering substances hardly produce any current change, indicating that the Co-TBTT modified electrode has excellent selectivity and anti-interference properties.

[0039] Furthermore, to evaluate the repeatability of the sensor, this experiment tested the response of six different batches of Co-TBTT / GCE electrodes to the same concentration of glucose. Figure 5 As shown in b, the RSD of the oxidation peak current is 2.03%, indicating good reproducibility. Figure 5As shown in Figure c, six consecutive measurements of the same electrode show an RSD of 0.72%, demonstrating its good operational stability.

Claims

1. Metal-organic framework materials based on bis(thienyl)octacarboxylic acid ligands, the structural formula of which is as follows:

2. The method for preparing a metal-organic framework material based on a dithienyl octacarboxylic acid ligand according to claim 1, characterized in that, Includes the following steps: Co(NO3)2·6H2O and octacarboxylated tetraphenylthiophene[3,2-b]thiophene (mass ratio 1.6:1) were dissolved in a solvent composed of DMA and H2O (volume ratio 2:1). After ultrasonic dissolution, acetic acid solution was added, and the mixture was placed in an oven at 100±10℃ for at least 48 h, then cooled to room temperature. The crystals were collected by filtration, washed with DMA and ethanol, and dried in a vacuum oven to obtain the metal-organic framework material.

3. The preparation method according to claim 2, characterized in that, The octacarboxylated tetraphenylthiophene[3,2-b]thiophene is prepared by the following steps: tetrabromodithiophene, 3,5-bis(methoxycarbonyl)phenylboronic acid, anhydrous cesium carbonate, and tetratriphenylphosphine palladium are added to a 350 mL reaction flask. After purging the reaction system with argon, ultra-dry 1,4-dioxane solvent is added under an argon atmosphere. The reaction system is stirred at 100°C for 48 hours. After the reaction is completed, the reaction system is cooled to room temperature, and the organic solvent of the reaction system is removed by rotary evaporation. The system is extracted with dichloromethane and water, the organic phase is collected, and anhydrous sodium sulfate is added to remove water. After rotary evaporation, a dark brown crude product is obtained. The crude product is hydrolyzed to obtain octacarboxylated tetraphenylthiophene[3,2-b]thiophene.

4. The preparation method according to claim 2, characterized in that, The filtration and collection, washing with DMA and ethanol are performed at least three times.

5. The preparation method according to claim 2, characterized in that, The concentration of the acetic acid solution is 6 mol / L.

6. The preparation method according to claim 2, characterized in that, The vacuum drying temperature is 65℃ and the time is 12h.

7. A glucose sensing electrode material based on the metal-organic framework material of the dithienyl octacarboxylic acid ligand as described in claim 1, characterized in that, Prepared by the following steps: The glassy carbon electrode (GCE) was polished with 0.05 µm alumina powder, then ultrasonically cleaned successively with anhydrous ethanol and ultrapure water, and allowed to air dry. The selected Co-TBTT sample was ground and ultrasonically dissolved in deionized water. 10 μL of a 1 mg / mL solution was then taken. -1 Co-TBTT solution was dropped onto the treated GCE surface and dried at room temperature. Then, Nation solution with a mass concentration of 0.05% was dropped onto the GCE surface to finally obtain the Co-TBTT / GCE modified electrode.

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